Background Households are hotspots for SARS-CoV-2 transmission. In the US, the COVID-19 pandemic has had a disproportionate impact on communities of color. Methods Between April-October 2020, the CO-HOST prospective cohort study enrolled 100 COVID-19 cases and 208 of their household members in North Carolina, including 44% who identified as Hispanic or non-white. Households were enrolled a median of 6 days from symptom onset in the index case. Incident secondary cases within the household were detected by quantitative PCR of weekly nasal swabs (days 7, 14, 21) or by seroconversion at day 28. Results Excluding 73 household contacts who were PCR-positive at baseline, the secondary attack rate among household contacts was 32% (33/103, 95% CI 22%-44%). The majority of cases occurred by day 7, with later cases confirmed as household-acquired by viral sequencing. Infected persons in the same household had similar nasopharyngeal viral loads (ICC=0.45, 95% CI 0.23-0.62). Households with secondary transmission had index cases with a median viral load that was 1.4 log10 higher than households without transmission (p=0.03) as well as higher living density (>3 persons occupying <6 rooms) (OR 3.3, 95% CI 1.02-10.9). Minority households were more likely to experience high living density and had a higher risk of incident infection than did white households (SAR 51% vs. 19%, p=0.01). Conclusions Household crowding in the context of high-inoculum infections may amplify the spread of COVID-19, potentially contributing to disproportionate impact on communities of color.

Background Few prospective studies of SARS-CoV-2 transmission within households have been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color. Methods and Findings This is a prospective observational study. Between April-October 2020, the UNC CO-HOST study enrolled 102 COVID-positive persons and 213 of their household members across the Piedmont region of North Carolina, including 45% who identified as Hispanic/Latinx or non-white. Households were enrolled a median of 6 days from onset of symptoms in the index case. Secondary cases within the household were detected either by PCR of a nasopharyngeal (NP) swab on study day 1 and weekly nasal swabs (days 7, 14, 21) thereafter, or based on seroconversion by day 28. After excluding household contacts exposed at the same time as the index case, the secondary attack rate (SAR) among susceptible household contacts was 60% (106/176, 95% CI 53%-67%). The majority of secondary cases were already infected at study enrollment (73/106), while 33 were observed during study follow-up. Despite the potential for continuous exposure and sequential transmission over time, 93% (84/90, 95% CI 86%-97%) of PCR-positive secondary cases were detected within 14 days of symptom onset in the index case, while 83% were detected within 10 days. Index cases with high NP viral load (>10^6 viral copies/ul) at enrollment were more likely to transmit virus to household contacts during the study (OR 4.9, 95% CI 1.3-18 p=0.02). Furthermore, NP viral load was correlated within families (ICC=0.44, 95% CI 0.26-0.60), meaning persons in the same household were more likely to have similar viral loads, suggesting an inoculum effect. High household living density was associated with a higher risk of secondary household transmission (OR 5.8, 95% CI 1.3-55) for households with >3 persons occupying <6 rooms (SAR=91%, 95% CI 71-98%). Index cases who self-identified as Hispanic/Latinx or non-white were more likely to experience a high living density and transmit virus to a household member, translating into an SAR in minority households of 70%, versus 52% in white households (p=0.05). Conclusions SARS-CoV-2 transmits early and often among household members. Risk for spread and subsequent disease is elevated in high-inoculum households with limited living space. Very high infection rates due to household crowding likely contribute to the increased incidence of SARS-CoV-2 infection and morbidity observed among racial and ethnic minorities in the US. Quarantine for 14 days from symptom onset of the first case in the household is appropriate to prevent onward transmission from the household. Ultimately, primary prevention through equitable distribution of effective vaccines is of paramount importance.

As the threat of arboviral diseases continues to escalate worldwide, the question of, “What types of human communities are at the greatest risk of infection?” persists as a key gap in the existing knowledge of arboviral diseases transmission dynamics. Here, we comprehensively review the existing literature on the socioeconomic drivers of the most common Aedes mosquito-borne diseases and Aedes mosquito presence/abundance. We reviewed a total of 182 studies on dengue viruses (DENV), chikungunya virus (CHIKV), yellow fever virus (YFVV), Zika virus (ZIKV), and presence of Aedes mosquito vectors. In general, associations between socioeconomic conditions and both Aedes -borne diseases and Aedes mosquitoes are highly variable and often location-specific. Although 50% to 60% of studies found greater presence or prevalence of disease or vectors in areas with lower socioeconomic status, approximately half of the remaining studies found either positive or null associations. We discuss the possible causes of this lack of conclusiveness as well as the implications it holds for future research and prevention efforts.

Climate change, urbanization, and globalization have facilitated the spread of Aedes mosquitoes into regions that were previously unsuitable, causing an increased threat of arbovirus transmission on a global scale. While numerous studies have addressed the urban ecology of Ae. albopictus, few have accounted for socioeconomic factors that affect their range in urban regions. Here we introduce an original sampling design for Ae. albopictus, that uses a spatial optimization process to identify urban collection sites based on both geographic parameters as well as the gradient of socioeconomic variables present in Mecklenburg County, North Carolina, encompassing the city of Charlotte, a rapidly growing urban environment. We collected 3645 specimens of Ae. albopictus (87% of total samples) across 12 weeks at the 90 optimized site locations and modelled the relationships between the abundance of gravid Ae. albopictus and a variety of neighborhood socioeconomic attributes as well as land cover characteristics. Our results demonstrate that the abundance of gravid Ae. albopictus is inversely related to the socioeconomic status of the neighborhood and directly related to both landscape heterogeneity as well as proportions of particular resident races/ethnicities. We present our results alongside a description of our novel sampling scheme and its usefulness as an approach to urban vector epidemiology. Additionally, we supply recommendations for future investigations into the socioeconomic determinants of vector-borne disease risk.

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Kabuki syndrome (KS) is a Mendelian Disorder of the Epigenetic Machinery (MDEM) caused by loss of function variants in either of two genes involved in the regulation of histone methylation, KMT2D (34–76%) or KDM6A (9–13%). Previously, representative neurobehavioral deficits of KS were recapitulated in a mouse model, emphasizing the role of KMT2D in brain development, specifically in ongoing hippocampal neurogenesis in the granule cell layer of the dentate gyrus. Interestingly, anxiety, a phenotype that has a known association with decreased hippocampal neurogenesis, has been anecdotally reported in individuals with KS. In this study, anxiety and behavior were assessed in a cohort of 60 individuals with molecularly confirmed KS and 25 unaffected biological siblings, via questionnaires (SCARED/GAS-ID and CBCL/ABCL). Participant age ranged from 4 to 43 years old, with 88.3% of participants having a pathogenic variant in KMT2D, and the rest having variants in KDM6A. In addition, data was collected on adaptive function and positive affect/quality of life in participants with KS using appropriate online surveys including ABAS-III and PROMIS Positive Affect. Survey scores were compared within the KS participants across age groups and between KS participants and their unaffected siblings. We found that children with KS have significantly higher anxiety scores and total behavior problem scores than their unaffected siblings (p = 0.0225, p &lt; 0.0001). Moreover, a large proportion of affected individuals (22.2% of children and 60.0% of adults) surpassed the established threshold for anxiety; this may even be an underestimate given many patients are already treated for anxiety. In this sample, anxiety levels did not correlate with level of cognitive or adaptive function in any KS participants, but negatively correlated with positive affect in children with KS (p = 0.0005). These findings indicate that anxiety is a common neurobehavioral feature of KS. Providers should therefore carefully screen individuals with KS for anxiety as well as other behavioral issues in order to allow for prompt intervention. Neurobehavioral anxiety measures may also prove to be important outcome measures for clinical trials in KS.

Kabuki syndrome (KS) is a rare epigenetic disorder caused by heterozygous loss of function variants in either KMT2D (90%) or KDM6A (10%), both involved in regulation of histone methylation. While sleep disturbance in other Mendelian disorders of the epigenetic machinery has been reported, no study has been conducted on sleep in KS. This study assessed sleep in 59 participants with KS using a validated sleep questionnaire. Participants ranged in age from 4 to 43 years old with 86% of participants having a pathogenic variant in KMT2D. In addition, data on adaptive function, behavior, anxiety, and quality of life were collected using their respective questionnaires. Some form of sleep issue was present in 71% of participants, with night-waking, daytime sleepiness, and sleep onset delay being the most prevalent. Sleep dysfunction was positively correlated with maladaptive behaviors, anxiety levels, and decreasing quality of life. Sleep issues were not correlated with adaptive function. This study establishes sleep disturbance as a common feature of KS. Quantitative sleep measures may be a useful outcome measure for clinical trials in KS. Further, clinicians caring for those with KS should consider sleep dysfunction as an important feature that impacts overall health and well being in these patients.

Background: Standard nasopharyngeal swab testing for SARS-CoV-2 detection by PCR is not always feasible due to limitations in trained personnel, personal protective equipment, swabs, PCR reagents, and access to cold chain and biosafety hoods. Methods: We piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including both standard polyester flocked swabs as well as 3D printed plastic lattice swabs, placed into either viral transport media or an RNA stabilization agent. Quantitative SARS-CoV-2 viral detection by RT-qPCR was compared to that obtained by nasopharyngeal sampling as the reference standard. Pooling specimens in the lab versus pooling swabs at the point of collection was also evaluated. Results: Among 275 participants, flocked nasal swabs identified 104/121 individuals who were PCR-positive for SARS-CoV-2 by nasopharyngeal sampling (sensitivity 87%, 95% CI 79-92%), mostly missing those with low viral load (<10^3 viral copies/uL). 3D-printed nasal swabs showed similar sensitivity. When nasal swabs were placed directly into an RNA stabilizer, the mean 1.4 log decrease in viral copies/uL compared to nasopharyngeal samples was reduced to <1 log, even when samples were left at room temperature for up to 7 days. Pooling sample specimens or swabs both successfully detected samples >102 viral copies/uL. Conclusions: Nasal swabs are likely adequate for clinical diagnosis of acute infections to help expand testing capacity in resource-constrained settings. When collected into an RNA preservative that also inactivates infectious virus, nasal swabs yielded quantitative viral loads approximating those obtained by nasopharyngeal sampling.